CASE REPORT Open Access

Adenosquamous carcinoma of the ampullaof Vater: a case report and literature reviewSojun Hoshimoto1*, Koichi Aiura1, Masaya Shito1, Toshihiro Kakefuda1 and Hitoshi Sugiura2

Abstract

Background: Adenosquamous carcinoma of the ampulla of Vater is extremely rare, and its clinicopathologicalfeatures are limited and described in few previous case reports. Here, we report curative resection ofadenosquamous carcinoma of the ampulla of Vater at an early stage.

Case presentation: An 81-year-old woman was referred to our hospital for investigation of the frequent elevationof hepatic and biliary enzymes and dilatation of the intrahepatic bile ducts. Preoperative examinations revealed anexposed reddish tumor in the ampulla of Vater, which was diagnosed on biopsy to be adenocarcinoma withsquamous cell carcinoma component. Pylorus-preserving pancreaticoduodenectomy with regional lymph nodedissection was performed. Pathological examinations revealed the presence of two malignant components in thelesion, including poorly differentiated tubular adenocarcinoma and squamous cell carcinoma, without invasionbeyond the sphincter of Oddi or into the duodenal submucosa. These squamous cell carcinoma andadenocarcinoma components in the tumor comprised approximately 30 and 70 % of the lesion, respectively. Nometastasis into regional lymph nodes was observed, and the patient experienced no tumor recurrence ormetastasis until 20 months after surgery.

Conclusion: We identified only six reported cases of adenosquamous carcinoma of the ampulla of Vater in theEnglish literature, and all of these patients died of recurrence within 14 months after surgery. To the best of ourknowledge, this is the first report of adenosquamous carcinoma of the ampulla of Vater that was curatively resectedat an early stage. Although more number of studies on clinicopathological findings are required to determine theappropriate surgical indication, we suggest that surgery remains the mainstay therapy for adenosquamouscarcinoma of the ampulla of Vater detected at an early stage.

Keywords: Adenosquamous carcinoma, Carcinoma of the ampulla of Vater, Pancreaticoduodenectomy

BackgroundAdenosquamous carcinoma (ASC) is characterized byvariable combinations of two malignant components, in-cluding adenocarcinoma and squamous cell carcinoma(SCC). Adenocarcinomas account for most malignanciesof the ampulla of Vater; however, ASC is a rare condi-tion. Although the proportion of the aforementionedtwo components varies, adenocarcinoma usually pre-dominates. According to the WHO classification of tu-mors of the digestive system, ASC is shown to compriseat least 25 % of the SCC component in the tumor [1].

ASCs in other primary sites that normally have glandu-lar epithelium, such as the pancreas, stomach, colon andrectum, breast, and prostate, are also rare and are consid-ered to be clinically more aggressive, with worse prognosisthan their adenocarcinoma counterparts [2–8]. Most stud-ies on ASC in the ampulla of Vater have been small seriesor single case reports because of its rarity. Therefore, clini-copathological features and outcomes of this entity remainunclear and no therapeutic strategies have been estab-lished. Here, we report a case of ASC of the ampulla ofVater that was curatively resected at an early stage, and re-view the reported cases of this unusual entity.

Case presentationAn 81-year-old Japanese woman with a medical historyof type II diabetes mellitus and arteriosclerosis obliterans

* Correspondence: sojunh@yahoo.co.jp1Department of Surgery, Kawasaki Municipal Hospital, Kawasaki 210-0013,Kanagawa, JapanFull list of author information is available at the end of the article

WORLD JOURNAL OF SURGICAL ONCOLOGY

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Hoshimoto et al. World Journal of Surgical Oncology (2015) 13:287 DOI 10.1186/s12957-015-0709-0

was referred to our hospital for investigation of the fre-quent elevation of hepatic and biliary enzymes and dila-tation of the intrahepatic bile ducts, which wereidentified by her family doctor during abdominal ultra-sonography. The patient did not complain of abdominalpain or decreased appetite. Laboratory examinations re-vealed slightly elevated biliary enzymes, including413 IU/L alkaline phosphatase (normal, 104–338 IU/L)and 184 IU/L γ-glutamyl transpeptidase (normal, 9–28 IU/L); however, other serum chemistry data werewithin normal limits. Levels of the serum tumor markerscarcinoembryonic antigen and carbohydrate antigen 19-9 were also within normal limits. Contrast-enhanced ab-dominal computed tomography and magnetic resonancecholangiopancreatography showed dilatation of theintra- and extrahepatic bile ducts and the main pancre-atic duct without any strictures (Fig. 1a), suggesting thepresence of an ampullary tumor. Neither lymph nodeenlargement nor metastasis was observed. Endoscopicultrasonography showed a hypoechoic mass of 9 × 9 mmin the ampulla of Vater (Fig. 1b). The tumor was locatedon the inside of the duodenal wall and had not invadedthe duodenal muscularis propria, pancreas, common bileduct terminal, or main pancreatic duct. Duodenoscopyrevealed a bulging oral protrusion because of the dilateddistal bile duct and an exposed reddish tumor at the am-pulla of Vater (Fig. 1c), which was diagnosed on biopsyto be adenocarcinoma with the SCC component. Endo-scopic retrograde cholangiopancreatography (ERCP)showed dilatation of the upstream bile duct and mainpancreatic duct, and ERCP followed by transpapillarybiliary intraductal ultrasonography revealed a hypoe-choic tumor confined within the ampullary portion ofthe duodenum, the common channel of the ampulla,and the ampullary portion of the bile duct area. How-ever, no extension into the ampullary portion of the pan-creatic duct or the distal bile duct was observed.Because the patient showed the onset of acute cholan-gitis secondary to ERCP, endoscopic retrograde biliarydrainage was performed using a plastic stent on the day

after ERCP. Based on these findings, the lesion was diag-nosed as early-stage carcinoma of the ampulla of Vaterwith the SCC component without extension along thedistal bile duct or main pancreatic duct. Subsequently,pylorus-preserving pancreaticoduodenectomy (PPPD)with regional lymph node dissection was performed.Macroscopic examinations revealed a whitish and solidexposed-type tumor, 11 × 8 mm in size in the ampulla ofVater (Fig. 2). Pathological examinations showed thepresence of two malignant components, including poorlydifferentiated tubular adenocarcinoma and SCC withoutinvasion beyond the sphincter of Oddi or into the duo-denal submucosa (Fig. 3a). SCC and adenocarcinomacomponents in the tumor comprised approximately 30and 70 % of the tumor mass, respectively. No regionallymph node metastases or lymphovascular or perineuralinfiltrations were observed. Immunohistochemistry (IHC)analyses of the squamous marker cytokeratin (CK)-5/6showed strong positive expression in the SCC componentand slight expression in the adenocarcinoma component(Fig. 3b). In contrast, the adenocarcinoma marker CK-7was strongly detected in the adenocarcinoma componentand weakly detected in the SCC component (Fig. 3c). Thepostoperative course was uneventful and the patient expe-rienced no tumor recurrence or metastasis until 20 monthsfollowing surgery.

DiscussionAlthough the histogenesis of ASC remains unclear, thefour prevailing hypotheses describe (1) pluripotent stemcells capable of inducing the malignant transformationof both cell types, (2) squamous metaplasia in the intes-tinal mucosa, (3) malignant squamous metaplastic trans-formation of the adenocarcinoma, and (4) collision ofthe two malignant tumors [9]. It is currently acceptedthat adenosquamous carcinomas may occur throughmetaplastic malignant squamous transformation ofadenocarcinomas [10]. Accordingly, in the presentpathological examination, the SCC component was het-erogeneously distributed and IHC staining for squamous

Fig. 1 a Magnetic resonance cholangiopancreatography showed dilatation of the intra- and extrahepatic bile ducts and the main pancreatic ductwithout any stricture. b Endoscopic ultrasonography showed a hypoechoic mass in the ampulla of Vater located on the inside of the duodenalwall without invasion of the duodenal muscularis propria. c Duodenoscopy revealed an exposed reddish tumor at the ampulla of Vater

Hoshimoto et al. World Journal of Surgical Oncology (2015) 13:287 Page 2 of 5

cell carcinoma and adenocarcinoma markers clearly sep-arated discrete SCC and adenocarcinoma components,with no bidirectional differentiation of individual tumorcells. Moreover, neither squamous metaplasia in the un-involved adjacent epithelium nor a transition from squa-mous metaplasia to squamous cell carcinoma could beidentified. These observations are consistent with thetheory of metaplastic malignant squamous transform-ation of an adenocarcinoma.PubMed was searched using the terms “ampulla,” “pa-

pilla,” or “Vater,” and “adenosquamous carcinoma” andsix reported cases of ASC of the ampulla of Vater wereretrieved from the English literatures [9, 11, 12]. Demo-graphic and clinical characteristics of all studied patients,including the present patient, are summarized in Table 1.The average age at diagnosis was 62.0 ± 17.4 years(range, 47–82), and five of seven patients (71 %) weremen. In the present case, carcinoma of the ampulla ofVater was diagnosed during the work-up for elevationsof serum hepatobiliary enzymes. All other patients pre-sented with symptoms such as abdominal pain and jaun-dice, which were similar to the symptoms of conventional

adenocarcinomas of the ampulla of Vater. Preoperativeendoscopic biopsy identified the SCC components in fourcases (57 %), whereas the diagnosis of ASC was made aftersurgical resection in three cases (43 %). Surgical proce-dures performed were pancreaticoduodenectomy, includ-ing PPPD, in six cases (86 %) and ampullectomy in onecase (14 %). The mean tumor size in the four cases withrelevant data was 26.8 ± 12.9 mm (range, 11–40), andlymph node metastases were identified in three of sixcases with relevant data (50 %). Overall survival in allseven cases ranged from 6 to 20 months, and six of sevenpatients survived within 14 months after surgical resec-tion. In contrast, the present case survived for 20 monthswithout any evidence of recurrence.ASC is regarded as a more clinically aggressive tumor

with less favorable prognosis than adenocarcinomas ofother origins [2–8]. Imaoka et al. [13] reported that themedian overall survival of patients with ASC of the pan-creas was nearly half that of patients with pancreaticductal adenocarcinomas. Prognosis of the reported casesof ASC of the ampulla of Vater except the present casewas poor; however, because of the limited number ofcases, more studies on clinicopathological findings arenecessary to analyze whether the prognosis of ASC wasless favorable than that of the conventional adenocarcin-omas of the ampulla of Vater as well as other origins.Few reports describe associations between the propor-

tion of SCC components and tumor progression [14].However, SCC components grow more aggressively thanadenocarcinoma components in animal models [15].Moreover, several studies report significantly shorterdoubling times of SCCs than adenocarcinomas [16, 17],suggesting that the proportion of SCC components inASC increases with tumor progression and may be asso-ciated with prognosis. Accordingly, two reported casesof ASC of the ampulla of Vater with predominant SCCcomponent died of recurrence within 10 months aftersurgery [9, 12]. However, the Ki-67 index of poorly dif-ferentiated SCC and adenocarcinoma components in thepresent case were 33 and 34 %, respectively, indicating asimilar proliferative potential of SCC and adenocarcin-oma components. Yang et al. [9] demonstrated no sur-vival benefits of surgical interventions and promoted

Fig. 2 Macroscopic findings. A whitish and solid exposed-typetumor, 11 × 8 mm in size, was observed in the ampulla of Vater

Fig. 3 Histopathological and immunohistochemical findings. a Hematoxylin and eosin staining. b CK5/6 was strongly expressed in the squamouscell carcinoma component. c CK7 was expressed in the adenocarcinoma component (original magnification ×15)

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chemoradiation as the first choice of treatment for ASCof the ampulla of Vater if the diagnosis of ASC could bemade before surgery. However, pathological observationsof the present case showed limited tumor invasionwithin the sphincter of Oddi and no evidence of regionallymph node metastasis or perineural or angiolymphaticinvasions. Moreover, the SCC component comprisedonly 30 % of the tumor, presumably resulting in contin-ued survival until 20 months after surgery without evi-dence of recurrence. Therefore, we suggest that surgeryremains the mainstay therapy for ASC of the ampulla ofVater, although diagnosis of the condition during theearly stages when the adenocarcinoma component pre-dominates over the SCC component is critical.

ConclusionsHere, we report an unusual case of ASC of the ampullaof Vater. The subsequent literature review revealed thatall the reported cases of ASC of the ampulla of Vatercarried poor prognosis. To the best of our knowledge,this is the first report of ASC of the ampulla of Vaterthat was curatively resected at an early stage. Because ofits rarity, more number of studies on clinicopathologicalfindings are required to determine the association be-tween the proportion of the tumor comprising SCC andprogression, clinical outcome, and appropriate surgicalindication. Nonetheless, the present case supports earlydetection and the use of surgery as the only curativetreatment option for this rare entity.

ConsentWritten informed consent was obtained from the patientto allow publication of this case report and any accom-panying images. A copy of the written consent is avail-able for review by the Editor-in-Chief of this journal.

AbbreviationsASC: Adenosquamous carcinoma; CK: Cytokeratin; ERCP: Endoscopicretrograde cholangiopancreatography; IHC: Immunohistochemistry;PPPD: Pylorus-preserving pancreaticoduodenectomy; SCC: Squamous cellcarcinoma.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsSH drafted the manuscript. SH and KA were in charge of the treatment ofthe patient and performed the operation. MS participated in the treatmentof the patient, and contributed to the collection of the clinical data. KA andTK reviewed and edited the manuscript. HS prepared pathological images.All authors read and approved the final manuscript.

AcknowledgementsWe thank the patient and her family who agreed to publish the clinical data.

Author details1Department of Surgery, Kawasaki Municipal Hospital, Kawasaki 210-0013,Kanagawa, Japan. 2Department of Pathology, Kawasaki Municipal Hospital,Kawasaki 210-0013, Kanagawa, Japan.

Received: 23 July 2015 Accepted: 22 September 2015

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Table 1 Reported cases of adenosquamous carcinoma of the ampulla of Vater in the English literature

Year Author Age Gender Symptom Size(mm)

Biopsy Treatment LNmets

UICCstage

Proportion ofSCC

Prognosis(months)

2002 Ueno 47 M Jaundice, generalfatigue

22 SCC PD (+) III 75 % 10 Dead

2013 Yang 64 M Jaundice, abdominalpain

34 ADC PD (+) IIB SCC>>ADC 6 Dead

2013 Yang 82 M Jaundice NM SCC (−) Ampullectomy (−) IB NM 14 Dead

2013 Yang 68 M Jaundice, abdominalpain

NM SCC (−) PD (+) III NM 7 Dead

2013 Yang 34 F Jaundice, abdominalpain

NM SCC (−) PD (−) III NM 10 Dead

2014 Kshirsagar 58 M Jaundice, abdominalpain

40 SCC PD NM NM NM NM

Presentcase

81 F No symptoms 11 ADC +SCC

PPPD (−) IA 30 % 20 Alive

SCC squamous cell carcinoma, ADC adenocarcinoma, PD pancreaticoduodenectomy, PPPD pylorus-preserving pancreaticoduodenectomy, NM not mentioned

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